DESCRIPTION: The investigator proposes to examine how the cell tropism of HIV-1 influences the success of virus transmission in humans using the hu-PBL-SCID mouse model. Macrophage-tropic (M-tropic) virus is more successfully transmitted, which may be due to more rapid and efficient virus entry. The investigator will block virus entry with IgG1-b12 or AOP-RANTES, which block access to CD4 and CCR5, respectively. The investigator will determine if virus isolates from nontransmitting partners of exposed, uninfected (EU) individuals are inefficiently transmitted. Multiple virus isolates from nontransmitting partners or control isolates will be injected into hu-PBL-SCID mice derived from normal or EU donors. The basis of any observed resistance to infection of hu-PBL-SCID mice generated from EU donors will be further studied by cell fractionation and analysis of chemokine levels. The investigator hypothesizes that macrophage-derived virus is most efficiently transmitted and macrophages are the preferred initial target cell for transmission. The investigator will follow the course of infection in hu-PBL-SCID mice infected with macrophage- versus CD4+ T cell-derived virus, test the infectivity of virus isolates on primary macrophages versus primary CD4+ T cells, test the transmission of virus isolates to EU hu-PBL-SCID mice with or without prior macrophage depletion, and test the transmission of poorly infectious HIV-1 isolates as infected CD4+ T cells versus infected macrophages. The investigator will vary the state of T cell activation and the ratio of naive to memory T cells and then track infection with closely related viruses differing only in cell tropism and coreceptor usage to determine the importance of cell activation to viral susceptibility and to determine whether M/T- and T-tropic isolates can infect or activate naive CD4+ T cells.